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Joyce Lebbink


Rini de Crom, Claire Wyman, Joyce Lebbink, Klaas Hermans
Email
j.lebbink@erasmusmc.nl
mm2m@erasmusmc.nl
Affiliations
Cell Biology & Genetics,
Erasmus University Medical Center
Rotterdam
Website
http://www.erasmusmc.nl/medical_genetics/
Expertise
My research interests focus on mechanistic and structural aspects of DNA mismatch repair. A central theme is how coordinated DNA and nucleotide binding controls intra- and intermolecular signaling and ultimately decides faithful repair of DNA damage. In particular I have studied in detail the correct initiation of MMR after detection of a DNA mismatch by E.coli MutS. We identified the role of a conserved hydrogen bond in intramolecular signaling between mismatch binding and ATPase domains of MutS (Lebbink et al, EMBO J., 2006). Currently we analyze the role of magnesium in relaying correct conformational changes within the MutS protein upon mismatch detection. We furthermore developed a high-resolution mass spectrometry assay that allows simultaneous detection of DNA mismatch binding and nucleotide binding by single MutS dimers (collaboration with Albert Heck, University of Utrecht). Currently we are studying the molecular mechanisms of DNA MMR using scanning force microscopy imaging to visualize the DNA conformational changes that occur upon mismatch repair protein complex formation and initiation of DNA unwinding.
Selected references
  • Lamers MH, Georgijevic D, Lebbink JH, Winterwerp HH, Agianian B, de Wind N, Sixma TK. ATP increases the affinity between MutS ATPase domains: Implications for ATP hydrolysis and conformational changes. J Biol Chem 2004 279:43879-43885
  • Lebbink JH, Georgijevic D, Natrajan G, Fish A, Winterwerp HH, Sixma TK, de Wind N. Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair. EMBO J 2006 25:409-419.